Effects of dapagliflozin in patients with nonalcoholic fatty liver disease:A systematic review and meta-analysis of randomized controlled trials

Background: Dapagliflozin as a treatment option in patients with nonalcoholic fatty liver disease (NAFLD) has received increasing attention, however, the efficacy and safety of dapagliflozin for NAFLD has not been well assessed. This meta-analysis aimed to summarize these RCTs and evaluate the efficacy of dapagliflozin for patients with NAFLD. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for RCTs comparing dapagliflozin with placebo or active comparator in patients with NAFLD from inception to Oct 2021. Results: We included seven trials with 390 randomized participants in total. Compared to the placebo or control group, dapagliflozin could reduce the levels of alanine aminotransferase(ALT) (WMD: -6.62U/L; 95%CI: -12.66, -0.58; p = 0.03) and aspartate aminotransaminase(AST) (WMD: -4.20U/L; 95%CI: -7.92, -0.47; p = 0.03). However, dapagliflozin produced a non-significant decrease in gamma-glutamyl transferase (GGT) levels (WMD: -7.28U/L; 95%CI: -16.26, 1.71; p = 0.11). Additionally, we showed that dapagliflozin significantly affect Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (WMD: -0.88; 95%CI: -1.43,-0.33; p = 0.002). Metabolic outcomes, such as bodyweight (WMD: -3.79 Kg; 95%CI: -4.63,-2.95; p < 0.00001), body mass index (BMI) (WMD: -1.33 Kg/m(2); 95%CI: -2.37,-0.28; p = 0.01), low-density lipoprotein cholesterol (LDL-C) (WMD: -2.66 mg/dL; 95%CI: -3.99, -1.32; p < 0.00001) and triglycerides (TG) (WMD: -16.77 mg/dL; 95%CI: -31.93, -1.61; p = 0.03) were also reduced. Meanwhile, we found that dapagliflozin increased total cholesterol (TC) (WMD: 9.77 mg/dL; 95%CI: 1.58, 17.97; p = 0.02). There was no significant difference in the incidence of total adverse events between the dapagliflozin group and the control group (RR = 0.96; 95%CI: 0.60, 1.54; p = 0.86). Conclusion: Our results suggest that dapagliflozin effectively improves liver function parameters and metabolic outcomes among patients with NAFLD. At the same time, treatment with dapagliflozin may increase total cholesterol. (C) 2022 Elsevier Masson SAS. All rights reserved.